背景：凡德他尼是一种小分子酪氨酸激酶抑制剂。它主要通过抑制血管内皮生长因子受体2来对一系列肺癌发挥治疗作用。然而，尚不清楚凡德他尼是否对其他肺部疾病（特别是哮喘）具有治疗作用。本研究调查了凡德他尼在哮喘治疗中的开创性用途。方法：体内实验主要通过建立哮喘模型、气道阻力测量和组织学分析来证实凡德他尼的抗收缩和抗炎作用，体外实验包括肌张力和全细胞贴片测量-钳记录，用于探索潜在的分子机制。结果：哮喘小鼠模型的体内实验表明，凡德他尼可以显着减轻全身炎症和一系列气道病理变化，包括过敏、分泌过多和重塑。随后的体外实验表明，凡德他尼能够通过钙动员来松弛小鼠气管的预收缩环，钙动员受到特定离子通道（包括VDLCC、NSCC、NCX和K通道）的调节。结论：综上所述，我们的研究证明凡德他尼在哮喘治疗中同时具有抗收缩和抗炎特性，这也表明凡德他尼通过减少异常气道收缩和全身炎症来治疗哮喘的可行性。版权所有 © 2024 Zeng 、薛、李、赵、陈、王、沉。

Background: Vandetanib is a small-molecule tyrosine kinase inhibitor. It exerts its therapeutic effects primarily in a range of lung cancers by inhibiting the vascular endothelial growth factor receptor 2. However, it remains unclear whether vandetanib has therapeutic benefits in other lung diseases, particularly asthma. The present study investigated the pioneering use of vandetanib in the treatment of asthma. Methods: In vivo experiments including establishment of an asthma model, measurement of airway resistance measurement and histological analysis were used primarily to confirm the anticontractile and anti-inflammatory effects of vandetanib, while in vitro experiments, including measurement of muscle tension and whole-cell patch-clamp recording, were used to explore the underlying molecular mechanism. Results: In vivo experiments in an asthmatic mouse model showed that vandetanib could significantly alleviate systemic inflammation and a range of airway pathological changes including hypersensitivity, hypersecretion and remodeling. Subsequent in vitro experiments showed that vandetanib was able to relax the precontracted rings of the mouse trachea via calcium mobilization which was regulated by specific ion channels including VDLCC, NSCC, NCX and K+ channels. Conclusions: Taken together, our study demonstrated that vandetanib has both anticontractile and anti-inflammatory properties in the treatment of asthma, which also suggests the feasibility of using vandetanib in the treatment of asthma by reducing abnormal airway contraction and systemic inflammation.Copyright © 2024 Zeng, Xue, Li, Zhao, Chen, Wang and Shen.